Molecular Modeling of Small Molecules as BVDV RNA-Dependent RNA Polymerase Allosteric Inhibitors

Abstract

Bovine viral diarrhea virus (BVDV), a major pathogen of cattle, is a well-characterized pestivirus which has been used as a good model virus for HCV. The RNA-dependent RNA polymerase (RdRp) plays a key role in the RNA replication process, thus it has been targeted for antivirus drugs. We employed two-dimensional quantitative structure-activity relationship (2D-QSAR) and molecular field analysis (MFA) to identify the molecular substructure requirements, and the particular characteristics resulted in increased inhibitory activity for the known series of compounds to act as effective BVDV inhibitors. The 2D-QSAR study provided the rationale concept for changes in the structure to have more potent analogs focused on the class of arylazoenamines, benzimidazoles, and acridine derivatives with an optimal subset of descriptors, which have significantly contributed to overall anti-BVDV activity. MFA represented the molecular patterns responsible for the actions of antiviral compound at their receptors. We conclude that the polarity and the polarizability of a molecule play a main role in the inhibitory activity of BVDV inhibitors in the QSAR modeling.

Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer’s Disease Agents Using Pharmacophore, 3D-QSAR, and Molecular Docking Approaches

“…Through the 3D-QSAR model, the relationship between steric or electrostatic molecular fields and activity can be described for guiding the further drug design. A molecule with negative electrostatic potential in the blue area and positive in the red area has a higher activity [ 23 ]. Similarly, the 3D view of model coefficients of van der Waals (VDW) interactions is also shown with two colors [ 24 ].…”

A combined in silico / in vitro approach unveils common molecular requirements for efficient BVDV RdRp binding of linear aromatic N-polycyclic systems

“…In this context, and in the framework of a long-lasting antiviral research program, our group designed and synthesized a series of new angular and linear N-polycyclic systems against representative ssRNA+ viruses. Small molecules inhibitors of BVDV has been reported in the literature with various scaffolds [17].…”

Chromium(III) and iron(III) inhibits replication of DNA and RNA viruses

“…The infection can cause a decrease in milk production, a reduced reproductive performance and growth retardation (Chai et al 2013). Infection in the early gestation period with BVDV may produce persistently infected calves that are responsible for the spread of virus in the herds (Kim et al 2009).…”

“…Symptoms of acute infection range from an inapparent to a severe course and can involve the respiratory, enteric, reproductive, immune and endocrine systems (Letellier and Kerkhofs 2003 ; Zhang et al 2014 ). The infection can cause a decrease in milk production, a reduced reproductive performance and growth retardation (Chai et al 2013 ). Infection in the early gestation period with BVDV may produce persistently infected calves that are responsible for the spread of virus in the herds (Kim et al 2009 ).…”